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Can authorities take advantage of the availability of generic atypical antipsychotic drugs? Findings from Sweden and potential implications
Introduction: Multiple reforms in Sweden appreciably enhanced prescribing efficiency for proton pump inhibitors, statins and renin-angiotensin inhibitor drugs. Potential exists to extend this to atypical antipsychotic drugs (AAPs), given their expenditure and oral generic risperidone available in Sweden from January 2009. However schizophrenia and bipolar disease are complex to treat and there is a need to tailor treatments, given the considerable inter-patient variability in responses and side-effects to different AAPs. Objectives: Assess changes in risperidone utilisation before and after oral generic risperidone reimbursed in January 2009 alongside any specific demand-side measures. In addition, to: (a) assess price reductions for risperidone over time and overall AAP expenditure; (b) suggest additional measures that could potentially be introduced; and (c) provide guidance to other European countries on the implications of any findings. Method: Principally a retrospective observational study and interrupted time series design. Key findings: No specific measures to encourage the prescribing of risperidone, and no appreciable change in its utilisation, after generics reimbursed. Oral risperidone was 96% generic, and its price 80% below pre-patent loss prices, by August 2011. This limited the increase in AAP expenditure compared with utilisation after generics. Conclusion: No apparent effectiveness or safety problems with generic risperidone. Authorities cannot rely on a spill-over from other disease areas to effect changes in physician prescribing habits. Specific measures are needed to encourage the prescribing of generic AAPs first line, where appropriate, exacerbated by the complexity of the disease areas. Their influence will be probably limited by the need to tailor treatment. © 2013 Royal Pharmaceutical Society.
Multi-cellular rosettes in the mouse visceral endoderm facilitate the ordered migration of anterior visceral endoderm cells
The visceral endoderm (VE) is a simple epithelium that forms the outer layer of the egg-cylinder stage mouse embryo. The anterior visceral endoderm (AVE), a specialised subset of VE cells, is responsible for specifying anterior pattern. AVE cells show a stereotypic migratory behaviour within the VE, which is responsible for correctly orientating the anterior-posterior axis. The epithelial integrity of the VE is maintained during the course of AVE migration, which takes place by intercalation of AVE and other VE cells. Though a continuous epithelial sheet, the VE is characterised by two regions of dramatically different behaviour, one showing robust cell movement and intercalation (in which the AVE migrates) and one that is static, with relatively little cell movement and mixing. Little is known about the cellular rearrangements that accommodate and influence the sustained directional movement of subsets of cells (such as the AVE) within epithelia like the VE. This study uses an interdisciplinary approach to further our understanding of cell movement in epithelia. Using both wild-type embryos as well as mutants in which AVE migration is abnormal or arrested, we show that AVE migration is specifically linked to changes in cell packing in the VE and an increase in multi-cellular rosette arrangements (five or more cells meeting at a point). To probe the role of rosettes during AVE migration, we develop a mathematical model of cell movement in the VE. To do this, we use a vertex-based model, implemented on an ellipsoidal surface to represent a realistic geometry for the mouse egg-cylinder. The potential for rosette formation is included, along with various junctional rearrangements. Simulations suggest that while rosettes are not essential for AVE migration, they are crucial for the orderliness of this migration observed in embryos. Our simulations are similar to results from transgenic embryos in which Planar Cell Polarity (PCP) signalling is disrupted. Such embryos have significantly reduced rosette numbers, altered epithelial packing, and show abnormalities in AVE migration. Our results show that the formation of multi-cellular rosettes in the mouse VE is dependent on normal PCP signalling. Taken together, our model and experimental observations suggest that rosettes in the VE epithelium do not form passively in response to AVE migration. Instead, they are a PCP-dependent arrangement of cells that acts to buffer the disequilibrium in cell packing generated in the VE by AVE migration, enabling AVE cells to migrate in an orderly manner. © 2012 Trichas et al.
Risk of venous thromboembolism in people with lung cancer: A cohort study using linked UK healthcare data
© 2016 Cancer Research UK. Background: Venous thromboembolism (VTE) is a potentially preventable cause of death in people with lung cancer. Identification of those most at risk and high-risk periods may provide the opportunity for better targeted intervention. Methods: We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics and Cancer Registry data. Our cohort comprises 10 598 people with lung cancer diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysis was performed to determine which demographic, tumour and treatment-related factors (time-varying effects of chemotherapy and surgery) independently affected VTE risk. We also determined the effect of a VTE diagnosis on the survival of people with lung cancer. Results: People with lung cancer had an overall VTE incidence of 39.2 per 1000 person-years (95% confidence interval (CI), 35.4-43.5), though rates varied depending on the patient group and treatment course. Independent factors associated with increased VTE risk were metastatic disease (hazard ratio (HR)=1.9, CI 1.2-3.0 vs local disease); adenocarcinoma subtype (HR=2.0, CI 1.5-2.7, vs squamous cell; chemotherapy administration (HR=2.1, CI 1.4-3.0 vs outside chemotherapy courses); and diagnosis via emergency hospital admission (HR=1.7, CI 1.2-2.3 vs other routes to diagnosis). Patients with VTE had an approximately 50% higher risk of mortality than those without VTE. Conclusions: People with lung cancer have especially high risk of VTE if they have advanced disease, adenocarcinoma or are undergoing chemotherapy. The presence of VTE is an independent risk factor for death.
© 2016 The Author(s). Background: Venous thromboembolism (VTE) is a well-recognised and life-threatening complication in patients with cancer. However, the precise risk of VTE in hospitalised cancer patients in England has not been previously reported. Methods: We conducted a cohort study using linked Hospital Episodes Statistics and Office for National Statistics mortality data. We determined the risk of VTE separately for 24 cancer sites following first hospitalisation for cancer (index date) and how this varied by age, proximity from hospital admission, administration of chemotherapy and calendar time. Results: Between 1998 and 2012, 3,558,660 patients were hospitalised for cancer. The cancer sites with the highest risk of VTE during initial hospitalisation for cancer were pancreatic (4.9 %), ovarian (4 %) and liver (3.8 %). The three cancer sites with the highest risk of first VTE event within 6 months from discharge were pancreatic (3.7 %), oesophagus (3 %) and stomach (2.8 %). For most cancers, the risk of VTE within 6 months from discharge was higher amongst patients who underwent chemotherapy compared to those who did not. The impact of age on risk of VTE varied considerably between cancer sites. Conclusions: The risk of VTE amongst patients hospitalised for cancer varies greatly by cancer site, age, proximity from hospital admission, and chemotherapy administration.
Aspirin and other non-steroidal anti-inflammatory drug use and colorectal cancer survival: A cohort study
Background: Aspirin has been widely reported to reduce the incidence of colorectal cancer. Recently, a survival benefit after diagnosis has also been suggested. Data regarding such a benefit are to date contradictory. This study examines the effect of non-steroidal anti-inflammatory drug (NSAID) use on mortality in colorectal cancer in a larger patient cohort than previously to further clarify this effect, especially in terms of exposure timing and dosing. Methods: A study using the General Practice Research Database assessed whether aspirin or NSAID exposure in the year immediately following diagnosis affected all-cause mortality in a cohort of 13 994 colorectal cancer patients. Cox proportional hazards modelling adjusted for age, gender, smoking, body mass index and comorbidity. Results: Overall mortality was slightly lower in patients treated with aspirin, (hazard ratio (HR)0.91; 95% confidence interval (CI)0.821.00). This effect was observed only in patients treated with prophylaxis-dose aspirin (HR0.89, CI0.800.98) and only in patients taking aspirin before diagnosis (HR0.86, CI0.760.98). Differential effects were observed depending on the time after diagnosis. Up to 5 years, a reduction in mortality was observed for aspirin users (HR0.83, CI0.750.92), whereas after 10 years there was an increase in mortality (HR1.94, CI1.262.99). For NSAID use, no significant effect was observed on overall mortality (HR1.07, CI0.981.15). High-dose NSAID use was associated with a slight increase in mortality (HR1.41, CI1.261.56).Interpretation:These findings provide further indication that aspirin may be beneficial in reducing mortality in colorectal cancer during the first 5 years. The same cannot be said for other NSAIDs, where a small increase in mortality was observed. © 2012 Cancer Research UK All rights reserved.
When are breast cancer patients at highest risk of venous thromboembolism? a cohort study using english health care data
© 2016 by The American Society of Hematology. Patients with breast cancer are at increased risk of venous thromboembolism (VTE), particularly in the peridiagnosis period. However, no previous epidemiologic studies have investigated the relative impact of breast cancer treatments in a time-dependentmanner. We aimed to determine the impact of breast cancer stage, biology, and treatment on the absolute and relative risks of VTE by using several recently linked data sources from England. Our cohort comprised 13 202 patients with breast cancer from the Clinical Practice Research Datalink (linked to Hospital Episode Statistics and Cancer Registry data) diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysiswas performedto determinewhichdemographic, treatment-related, and biological factors independently affected VTE risk.Women had an annual VTE incidence of 6% while receiving chemotherapywhichwas 10.8-fold higher (95% confidence interval [CI], 8.2-14.4; absolute rate [AR], 59.6 per 1000 person-years) than that in women who did not receive chemotherapy. After surgery, the riskwas significantly increased in the firstmonth (hazard ratio [HR], 2.2; 95% CI, 1.4-3.4; AR, 23.5; reference group, no surgery), but the risk was not increased after the first month. Risk of VTE was noticeably higher in the 3 months after initiation of tamoxifen compared with the risk before therapy (HR, 5.5; 95% CI, 2.3-12.7; AR, 24.1); however, initiating therapy with aromatase inhibitors was not associated with VTE (HR, 0.8;95%CI, 0.5-1.4;AR, 28.3). Inconclusion,womenreceivingchemotherapyfor breastcancerhaveaclinicallyimportant risk ofVTE, whereas an increased risk of VTE immediately after endocrine therapy is restricted to tamoxifen.
Background:Several studies suggest links between cancer and tricyclic antidepressant use.Methods:A case-control study using the General Practice Research Database examined whether previous tricyclic usage was associated with reduced incidence of brain (with glioma as a sub-category), breast, colorectal, lung and prostate cancers. Conditional logistic regression adjusted for age, gender, general practice, depression, smoking, body mass index, alcohol use and non-steroidal anti-inflammatory drug use.Results:A total of 31 953 cancers were identified, each matched with up to two controls. We found a statistically significant reduction in tricyclic prescriptions compared with controls in glioma (odds ratio (OR) 0.59, 95% confidence interval (CI)0.42-0.81) and colorectal cancer patients (OR0.84, CI0.75-0.94). These effects were dose-dependent (P-values for trend, glioma0.0005, colorectal0.001) and time-dependant (P-values for trend glioma0.0005, colorectal0.0086). The effects were cancer-type specific, with lung, breast and prostate cancers largely unaffected by antidepressant use.Conclusion:The biologically plausible, specific and dose- and time-dependant inverse association that we have found suggests that tricyclics may have potential for prevention of both colorectal cancer and glioma. © 2011 Cancer Research UK All rights reserved.
Background: Tricyclic antidepressants have been demonstrated in the laboratory to have anticancer properties. A recent study by our group also suggested a protective effect against development of colorectal cancer and glioma. This study aims to determine whether the anticancer action of tricyclics translates to improved survival in these cancers post-diagnosis. Methods: A study using the General Practice Research Database examined whether tricyclic antidepressant exposure in the months following diagnosis of glioma or colorectal cancer would affect longer term all-cause mortality. Cox proportional hazards modelling adjusted for age, gender, smoking, body mass index, comorbidity, and diagnosed depression. Results: A cohort of 1,364 glioma and 16,519 colorectal cancer patients were identified. There was a non-significant reduction in the hazard for glioma patients treated with tricyclics (HR = 0.83, CI = 0.53-1.30). This was mainly found in patients who were not previously exposed to tricyclics (HR = 0.56, CI = 0.26-1.18). In contrast, a significant increase in hazard was found for colorectal cancer (HR = 1.37, CI = 1.21-1.54). This was mostly in patients prescribed low-dose tricyclics (HR = 1.57, CI = 1.33-1.86). Conclusions: We have shown no significant mortality reduction in colorectal cancer or glioma patients treated with tricyclics. An apparent detrimental effect observed in colorectal cancer may be related to prescription of low-dose tricyclics in the management of pain related to disseminated cancer. We cannot rule out small effects or an effect that occurs exclusively at higher doses. Blinded clinical studies may therefore be the only method of determining efficacy in glioma patients. © 2012 Springer Science+Business Media Dordrecht.
Angiotensin converting enzyme inhibitors and hepatocellular carcinoma incidence in the General Practice Research Database
Objective: Laboratory findings demonstrate anticancer effects of angiotensin converting enzyme (ACE) inhibitors, including anti-angiogenic activity and inhibition of liver cancer growth in rodent models. Small studies in humans indicate potential for therapeutic anticancer effects and warrant further larger studies. Methods: A case-control study using the General Practice Research Database examined whether prior ACE inhibitor usage was associated with a reduction in incidence of hepatocellular carcinoma (HCC). Results: Two hundred twenty-four HCC cases were identified, each matched to up to 10 controls by age, sex, and general practice. The data show that HCC is associated with a small, nonsignificant increase in prior use of ACE inhibitors (OR = 1.16, CI = 0.67-2.00). ACE inhibitor use was 7.1% (of 224) in cases and 5.9% (of 2,313) in controls. No significant effects were found when investigating the effect of dose and exposure duration. Conclusions: We found no clear protective effect of ever or long term use of ACE inhibitors against the development of HCC. Our study suggests that it is unlikely that this class of drugs will be a clinically useful cancer chemoprevention therapy. © 2011 Springer Science+Business Media B.V.
© 2015 Elsevier Inc. All rights reserved. Background/purpose The purpose of the study was to determine absolute and relative rates of venous thromboembolism (VTE) following general surgical procedures in children compared to the general population. Methods We analyzed data from all patients under the age of 18 years in the Clinical Practice Research Datalink, linked to Hospital Episode Statistics from England (2001-2011) undergoing a general surgical procedure and population controls. Crude rates of VTE and adjusted hazard ratios were calculated using Cox regression. Results We identified 15,637 children who had a surgical procedure with 161,594 controls. Six children undergoing surgery had a VTE diagnosed in the year after compared to five children in the population cohort. The overall rate of VTE following surgery was 0.4 per 1000 person years (pyrs) (95% confidence interval [CI] 0.15-0.88) compared to 0.04 per 1000 pyrs (95% CI 0.02-0.09) in the population cohort. This represented a 9 fold increase in risk compared to the population cohort (adjusted hazard ratio [HR] 8.80; 95% CI 2.59-29.94). Conclusions Children are at increased risk for VTE following general surgical procedures compared to the general population however the absolute risk is small and given this the benefits of thromboprophylaxis need to be balanced against the risk of complications following its use.
Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis
© 2016 European Association for the Study of the Liver Background & Aims Direct-acting antivirals have become widely used for patients with chronic hepatitis C virus infection with decompensated cirrhosis. Virological responses are excellent and early improvements in liver function, at least in a proportion of patients, have been observed but the longer term impact of viral clearance on end-stage liver disease complications is unclear. Methods Prospective study of patients with decompensated cirrhosis who received 12 weeks of all-oral direct-acting antivirals through the English Expanded Access Programme. Endpoints were deaths, liver transplantation, hepatocellular carcinoma, serious decompensation events, sepsis or hospitalisations, and MELD scores between start of therapy to 15 months post-treatment start. An untreated cohort of patients was retrospectively studied over 6 months for comparison. Results Amongst 317/406 patients who achieved sustained virological response at 24 weeks post-treatment, there were 9 deaths (3%), 17 new liver cancers (5%), 39 transplantations (12%) and 52 with serious decompensations (16%), over 15 months. When compared to the first six months from treatment start and to untreated patients, there was a reduction in incidence of decompensations [30/406 (7%) in months 6–15 and 72/406 (18%) in months 0–6 for treated patients vs. 73/261 (28%) in untreated patients]. There was no significant difference in liver cancer incidence (10/406 (2.5%) in months 6–15 and 17/406 (4%) in months 0–6 for treated patients vs. 11/261 (4%) in untreated patients). Conclusions This study suggests that antiviral therapy in patients with decompensated cirrhosis led to prolonged improvement in liver function, with no evidence of paradoxical adverse impact nor increase in liver malignancy. Lay summary This is a report of a large group of patients in England who have hepatitis C virus (HCV) infection with advanced liver disease. They have been treated with new anti-HCV drugs, which cured the infection in the majority. This study looks at their outcomes a year following treatment, in terms of deaths, cancers and other complications of advanced liver disease. We conclude that in most patients anti-HCV treatment is beneficial even in advanced liver disease.
5-Fluorouracil chemotherapy affects spatial working memory and newborn neurons in the adult rat hippocampus
Chemotherapy-associated memory deficits in adults are prevalent with systemic treatment utilizing 5-fluorouracil (5-Fu). 5-Fu disrupts cell proliferation and readily crosses the blood-brain barrier. Proliferating cells within the adult dentate gyrus of the hippocampus give rise to new neurons involved in memory and learning and require neurotrophic factors such as brain-derived neurotrophic factor (BDNF) to nurture this process of adult neurogenesis. Some of these proliferating cells are anatomically and functionally supported by vascular endothelial cells. We propose that systemically administered 5-Fu chemotherapy will cause deficits in hippocampal memory that are associated with altered BDNF levels and proliferating cells (particularly vascular-associated cells) in the dentate gyrus. This was tested by determining the effect of 5-Fu on spatial working memory as modelled by the object location recognition test. Numbers of vascular-associated (VA) and non-vascular-associated (NVA) proliferating cells in the dentate gyrus were measured using double-labelling immunohistochemistry with markers of proliferation (Ki67) and endothelial cells (RECA-1). 5-Fu-induced changes in hippocampal BDNF and doublecortin (DCX) protein levels were quantified using Western immunoblotting. 5-Fu chemotherapy caused a marginal disruption in spatial working memory and did not alter the total proliferating cell counts or the percentage of VA and NVA proliferating cells in the dentate gyrus. In contrast, 5-Fu significantly reduced BDNF and DCX levels in the hippocampus, indicating alterations in neurotrophin levels and neurogenesis. These findings highlight the usefulness of animal models of 'chemobrain' for understanding the mechanisms that underlie chemotherapy-associated declines in cognitive performance and memory. © The Authors (2008).
Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis
© 2016 European Association for the Study of the Liver. Background & Aims All oral direct acting antivirals (DAAs) effectively treat chronic hepatitis C virus (HCV) infection, but the benefits in advanced liver disease are unclear. We compared outcomes in treated and untreated patients with decompensated cirrhosis. Methods Patients with HCV and decompensated cirrhosis or at risk of irreversible disease were treated in an expanded access programme (EAP) in 2014. Treatment, by clinician choice, was with sofosbuvir, ledipasvir or daclatasvir, with or without ribavirin. For functional outcome comparison, untreated patients with HCV and decompensated cirrhosis who were registered on a database 6 months before treatment was available were retrospectively studied. Primary endpoint was sustained virological response 12 weeks post antiviral treatment (treated cohort) and the secondary endpoint (both cohorts) was adverse outcomes (worsening in MELD score or serious adverse event) within 6 months. Results 467 patients received treatment (409 decompensated cirrhosis). Viral clearance was achieved in 381 patients (81.6%) - 209 from 231 (90.5%) with genotype 1 and 132 from 192 (68.8%) with genotype 3. MELD scores improved in treated patients (mean change -0.85) but worsened in untreated patients (mean + 0.75) (p <0.0001). Patients with initial serum albumin <35 g/L, aged >65 or with low (<135 mmol/L) baseline serum sodium concentrations were least likely to benefit from therapy. Conclusions All oral DAAs effectively cured HCV in patients with advanced liver disease. Viral clearance was associated with improvement in liver function within 6 months compared to untreated patients. The longer term impact of HCV treatment in patients with decompensated cirrhosis remains to be determined.
Incidence of venous thromboembolism in patients with cancer-A cohort study using linked United Kingdom databases
Background: Accurate population-based data are needed on the incidence of venous thromboembolism (VTE) in patients with different cancers in order to inform guidelines on which hospitalised and ambulatory cancer patients should receive VTE prophylaxis. Methods: We conducted a cohort study using data from the Clinical Practice Research Datalink, linked to Hospital Episode Statistics, Cancer Registry data and Office for National Statistics cause of death data. We determined the incidence rates (cases per 1000 person-years) of VTE separately for 24 cancer sites. To determine relative risk, incidence rates were compared to frequency-matched controls (by age) with no record of cancer. Findings: We identified 83,203 cancer patients and 577,207 controls. New cases of VTE were diagnosed in 3352 cancer patients, and 6353 controls. The absolute rate of VTE in all cancers was 13.9 per 1000 person-years (95% confidence interval [CI] 13.4-14.4), corresponding to an age, sex and calendar year adjusted hazard-ratio of 4.7 (CI 4.5-4.9) between cancer patients and the general population. Rates varied greatly by cancer site (range; 98 (CI 80-119) in pancreatic cancer to 3.1 (CI 1.5-6.5) in thyroid cancer), age (range; 16.9 for patients over 80 years to 4.9 for those under 30 years) and time from diagnosis (range; 75 in the first three months to 8.4, >1 year after diagnosis). Interpretation: VTE is strongly linked to cancer, but the annual rate varies greatly by cancer site, proximity to diagnosis and age. Prophylaxis guidelines should take account of cancer site and such intervention should also be targeted towards the three months following diagnosis. © 2012 Elsevier Ltd. All rights reserved.
© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd. Background Appendicectomy is the commonest intra-abdominal emergency surgical procedure, and little is known regarding the magnitude and timing of the risk of venous thromboembolism (VTE) after surgery. This study aimed to determine absolute and relative rates of symptomatic VTE following emergency appendicectomy. Methods A cohort study was undertaken using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data of patients who had undergone emergency appendicectomy from 2001 to 2011. Crude rates and adjusted incidence rate ratios (IRRs) for VTE were calculated using Poisson regression, compared with baseline risk in the year before appendicectomy. Results A total of 13 441 patients were identified, of whom 56 (0·4 per cent) had a VTE in the first year after surgery. The absolute rate of VTE was highest during the in-hospital period, with a rate of 91·29 per 1000 person-years, which was greatest in those with a length of stay of 7 days or more (267·12 per 1000 person-years). This risk remained high after discharge, with a 19·1- and 6·6-fold increased risk of VTE in the first and second months respectively after discharge, compared with the year before appendicectomy (adjusted IRR: month 1, 19·09 (95 per cent c.i. 9·56 to 38·12); month 2, 6·56 (2·62 to 16·44)). Conclusion The risk of symptomatic VTE following appendicectomy is relatively high during the in-hospital admission and remains increased after discharge. Trials of extended thromboprophylaxis are warranted in patients at particularly high risk.
Introduction Cancer is a known risk factor for venous thromboembolism (VTE) in adults, but population-based data in children are scarce. Materials and methods We conducted a cohort study utilising linkage of the Clinical Practice Research Database (primary care), Hospital Episodes Statistics (secondary care), UK Cancer Registry data and Office for National Statistics cause of death data. From these databases, we selected 498 children with cancer diagnosed between 1997 and 2006 and 20,810 controls without cancer. We calculated VTE incidence rates in children with cancer vs. controls, and hazard ratios (HRs) using Cox regression. Results We identified four VTE events in children with cancer compared with four events in the larger control population corresponding to absolute risks of 1.52 and 0.06 per 1000 person-years respectively. The four children with VTE and cancer were diagnosed with hematological, bone or non-specified cancer. Childhood cancer was hence associated with a highly increased risk of VTE (HR adjusted for age and sex: 28.3; 95%CI = 7.0-114.5). Conclusions Children with cancer are at increased relative risk of VTE compared to those without cancer. Physicians could consider thromboprophylaxis in children with cancer to reduce their excess risk of VTE however the absolute risk is extremely small and the benefit gained therefore would need to be balanced against the risk invoked of implementing such a strategy. Novelty & Impact Statements While there is a reasonable level of knowledge about the risk of VTE in adult populations, it is not well known whether this risk is reflected in paediatric patients. We found a substantial increase in risk of VTE in children with cancer compared to a child population without cancer. While this finding is important, the absolute risk of VTE is still low and must be balanced with the risks of anticoagulation. © 2014 The Authors.
© 2016 Wolters Kluwer Health, Inc. Laboratory studies have suggested that adrenergic blockers may inhibit the proliferation and migration of cancer cells, but epidemiological evidence of their effect on cancer incidence has proven inconsistent. We therefore conducted a case-control study using the Clinical Practice Research Datalink to assess the effect of adrenergic blockers on the incidence of prostate, lung, bowel and breast cancers. From among patients aged 18 years or older who contributed at least 2 years of prospectively gathered data between 1 January 1987 and 31 December 2012, we selected incident cases of relevant cancers and controls, frequency matched 10: 1 by age. Logistic regression was used to adjust effect estimates for age, sex, smoking, alcohol use, and a number of potentially confounding comorbidities and coprescriptions. A total of 18 968 colorectal, 19 082 lung, 21 608 prostate and 29 109 breast cancers were identified. We found no evidence of a protective effect of adrenergic blockade in lung and prostate cancers and found a slightly increased risk for colorectal and breast cancers in users. This was largely explained by the effects of confounding in multivariate analyses, with final odds ratio estimates for lung, colorectal, breast and prostate cancers of 0.99 [95% confidence interval (0.96-1.04)], 1.14 (1.09-1.18), 1.10 (1.06-1.14), and 1.01 (0.98-1.05), respectively, for β-blocker exposure, and final odds ratio estimates for lung, colorectal and breast cancer of 1.03 (0.97-1.09), 1.13 (1.07-1.20), and 1.08 (1.00-1.17), respectively, for α-blocker exposure. We found no evidence to suggest that adrenergic blocker use prevents common cancers. Indeed, we found a slightly increased risk for colorectal and breast cancers, which may reflect residual confounding.
Building analytic skills to drive improvements in patient care and organisational decision making: An information analysts' development programme
© 2015 Emerald Group Publishing Limited. Purpose - This paper briefly outlines a development programme designed to improve the skills of NHS Information Analysts and assesses the extent these skills have been developed. There are significant opportunities for the NHS to utilise information more effectively, and Analysts have a key role. However, training opportunities prior to the development of this programme have been limited for this professional group. The purpose of this paper is to explore the potential benefits to the organisations, patients and the NHS as a whole, that improvements in the quality of analysis can deliver. Design/methodology/approach - The authors compared pre-course and post-course self-assessment of skill levels of Analysts who attended the programme. The authors also considered general feedback and comments from participants. Findings - All of the 40 skills areas assessed demonstrated an increase in mean competency score. In cohorts 1 and 2, 38 of these were statistically significant (p < 0.001-0.041, mean increase in score 1.0). For cohorts 3-5, 37 were statistically significant (p < 0.001-0.012; mean increase 1.2). These findings were supported by the positive feedback from participants. Practical implications - The programme develops skills for NHS Information Analysts which can improve the quality of analysis in the NHS, offering significant potential to improve the effectiveness and efficiency of healthcare. Originality/value - The Information Analysts' Development Programme provides the only training programme available for NHS Information Analysts, contributing to the development of data driven service improvement within the NHS. This may harness the power contained within data to drive improvement and ensure patients receive the highest quality of care.
Causes of death in people with liver cirrhosis in England compared with the general population: A population-based cohort study
OBJECTIVES: There is a need for unbiased estimates of cause-specific mortality by etiology in patients with liver cirrhosis. The aim of this study is to use nationwide linked electronic routine healthcare data from primary and secondary care alongside the national death registry data to report such estimates. METHODS: We identified from the linked Clinical Practice Research Datalink (CPRD) and English Hospital Episode Statistics adults with an incident diagnosis of liver cirrhosis linked to the Office for National Statistics between 1998 and 2009. Age-matched controls from the CPRD general population were selected. We calculated the cumulative incidence (adjusting for competing risks) and excess risk of death by 5 years from diagnosis for different causes of death, stratified by etiology and stage of disease. RESULTS: Five thousand one hundred and eighteen patients with cirrhosis were matched to 152,903 controls. Among compensated patients, the 5-year excess risk of liver-related death was higher than that of any other cause of death for all patients, except those of unspecified etiology. For example, those of alcohol etiology had 30.8% excess risk of liver-related death (95% confidence interval (CI): 27.9%, 33.1%) compared with 9.9% excess risk of non-liver-related death. However, patients of unspecified etiology had a higher excess risk of non-liver-related compared with liver-related death (10.7% vs. 6.7%). This was due to a high excess risk of non-liver neoplasm death (7.7%, 95% CI: 5.9%, 9.5%). All decompensated patients had a higher excess of liver-related mortality than any other cause. CONCLUSIONS: In order to reduce associated mortality among people with liver cirrhosis, patients' care pathways need to be tailored depending on the etiology and stage of the disease.